Hemochromatosis Gene Mutations: Prevalence and Effects on Pegylated-Interferon and Ribavirin Therapy Response in Chronic Hepatitis C in Sardinia

Sini, Margherita; Sorbello, Orazio; Civolani, Alberto; Demelia, Luigi

doi:10.1016/j.jceh.2012.06.004

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…Therefore, HFE gene mutations may act synergically with CHC in the development of liver damage, predicting a higher rate of nonresponse to therapy. Our results correlate with those of Sini et al, 13 who stated that 69 CHC patients with end-of-treatment response were lower among patients with HFE gene mutations compared with those with HFE gene wildtype (p = 0.005) and TSI showed a significant statistical difference between HFE mutant patients (50%) and wild-type homozygotes (43.4%) (p < 0.01). Coelho-Borges et al 14 had similar results in 2002 when they studied 44 Brazilian patients.…”

Section: Discussionsupporting

confidence: 91%

Hemochromatosis Gene Polymorphism as a Predictor of Sustained Virological Response to Antiviral Treatment in Egyptian Chronic Hepatitis C Patients

Mehrez¹,

Fattah

Azeem

et al. 2016

Euroasian Journal of Hepato-Gastroenterology

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Aim:The aim of this article is to assess HFE C282Y gene mutations as a predictor of sustained virological response (SVR) to anti-hepatitis C virus (HCV) treatment in Egyptian patients.Materials and methods:One hundred and forty chronic hepatitis C (CHC) patients were divided into two groups: 70 patients achieved SVR and 70 patients were nonresponders (NRs). All patients were subjected to quantitative polymerase chain reaction (PCR) at baseline, 12 and 24 weeks after therapy commencement. Deoxyribonucleic acid (DNA) sequencing for HFE (C282Y) was done by restriction fragment length polymorphism PCR.Results:Sixty five patients did not have mutation and 5 patients had C282Y mutation (GA) with SVR. While 45 NRs had heterozygous C282Y mutation (GA), 4 patients (5.7%) had homozygous mutation (AA) and 21 patients (30%) had no mutation (GG). The parameters of elevated iron [transferrin saturation (TS; p < 0.001), S iron (p < 0.02), total iron binding capacity (TIBC; p < 0.001), transferrin (p < 0.016), and soluble transferrin receptor (sTfR; p-value, 0.001)] were significantly associated with C282Y mutation. However, there was no significant difference regarding ferritin values and C282Y mutation in NR patients.Conclusion:Iron overload was frequently detected in CHC patients and associated with C282Y mutation, while biochemical markers of iron overload and C282Y HFE mutation were negative prognostic factor.How to cite this article: Mehrez MI, Fattah DSA, Azeem NAA, Saleh MA, Mostafa KM. Hemochromatosis Gene Polymorphism as a Predictor of Sustained Virological Response to Antiviral Treatment in Egyptian Chronic Hepatitis C Patients. Euroasian J Hepato-Gastroenterol 2017;7(2):154-157.

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Section: Discussionsupporting

confidence: 91%

Hemochromatosis Gene Polymorphism as a Predictor of Sustained Virological Response to Antiviral Treatment in Egyptian Chronic Hepatitis C Patients

Mehrez¹,

Fattah

Azeem

et al. 2016

Euroasian Journal of Hepato-Gastroenterology

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“…Human leukocyte antigen-H impacts HCV disease severity and treatment outcome as chronic HCV patients with HFE mutations often have more transferrin saturation and advanced liver fibrosis. For instance, only 27.5% of HFE-mutated carriers achieved response at the end of treatment with pegylated-interferon and ribavirin, as compared to 60% of non-carriers ( 318 ), suggesting that individuals with HFE mutations may be more susceptible to chronic HCV due to iron accumulation. In agreement, patients heterozygous for HH infected with HCV displayed higher liver fibrosis than those who were homozygous wildtype, providing additional support that iron dysregulation is a critical component of liver fibrosis ( 319 , 320 ).…”

Section: Nef-mediated Downregulation Of Hla-h Expression Contributes mentioning

confidence: 99%

Human Leukocyte Antigen (HLA) and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

2017

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The genetic factors associated with susceptibility or resistance to viral infections are likely to involve a sophisticated array of immune response. These genetic elements may modulate other biological factors that account for significant influence on the gene expression and/or protein function in the host. Among them, the role of the major histocompatibility complex in viral pathogenesis in particular human immunodeficiency virus (HIV) and hepatitis C virus (HCV), is very well documented. We, recently, added a novel insight into the field by identifying the molecular mechanism associated with the protective role of human leukocyte antigen (HLA)-B27/B57 CD8+ T cells in the context of HIV-1 infection and why these alleles act as a double-edged sword protecting against viral infections but predisposing the host to autoimmune diseases. The focus of this review will be reexamining the role of classical and non-classical HLA alleles, including class Ia (HLA-A, -B, -C), class Ib (HLA-E, -F, -G, -H), and class II (HLA-DR, -DQ, -DM, and -DP) in immune regulation and viral pathogenesis (e.g., HIV and HCV). To our knowledge, this is the very first review of its kind to comprehensively analyze the role of these molecules in immune regulation associated with chronic viral infections.

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“…The homozygous or heterozygous mutation of HFE C282Y causes hepatic iron overload which promotes steatosis and liver fibrosis in HCV‐infected patients . Similarly deleterious influence of HFE C282Y and H63D mutations has been shown in chronic hepatitis B and in NASH .…”

Section: The Hemochromatosis Gene (Hfe) Modulates Liver Iron Overloadmentioning

confidence: 99%

Impact of iatrogenic iron overload on the course of hepatitis C in the dialysis population: A plea for caution

Rostoker

Vaziri

2017

Hemodialysis International

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About 2.5% of the world population, corresponding to about 177 million individuals, are infected by hepatitis C virus (HCV), a small, single-stranded RNA virus. The prevalence of HCV infection among dialysis patients in Japan, Europe, and North America during the 2012 to 2015 period was found to be 8.7% in the DOPPS study. Nosocomial HCV spread in hemodialysis facilities still occurs. Increased hepatic tissue iron has been shown to play a deleterious role in the course of hepatitis C, favor development of fibrosis and cirrhosis and possibly increase the risk of liver cancer in the general population. Regular loss of blood in the hemodialysis circuit, in routine blood sampling for laboratory tests (for uremia monitoring), and in gut due to uremic enteropathy, invariably results in iron deficiency for which patients are commonly treated with intravenous (IV) iron preparations. Data on the effects of IV iron in hemodialysis patients with hepatitis C are limited (2 studies) and strongly suggest that parenteral iron may contribute to hepatocellular injury.Iatrogenic iron overload is extremely prevalent among hemodialysis population worldwide. Iron overload and toxicity has emerged as one of the most controversial topic in the management of anemia in dialysis patients. Given the known impact of iron in promoting growth and virulence of HCV and the associated liver disease, it is necessary to use iron therapy cautiously and closely monitor plasma markers of iron metabolism and liver iron stores non-invasively by means of MRI to avoid iron overload in this vulnerable population.

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Hemochromatosis Gene Mutations: Prevalence and Effects on Pegylated-Interferon and Ribavirin Therapy Response in Chronic Hepatitis C in Sardinia

Cited by 4 publications

References 37 publications

Hemochromatosis Gene Polymorphism as a Predictor of Sustained Virological Response to Antiviral Treatment in Egyptian Chronic Hepatitis C Patients

Hemochromatosis Gene Polymorphism as a Predictor of Sustained Virological Response to Antiviral Treatment in Egyptian Chronic Hepatitis C Patients

Human Leukocyte Antigen (HLA) and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

Impact of iatrogenic iron overload on the course of hepatitis C in the dialysis population: A plea for caution

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